article evidence for selective executive function deficits...
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Article
Evidence for selective executive function deficits in ecstasy/polydrug users
Fisk, John and Montgomery, C.
Available at http://clok.uclan.ac.uk/1191/
Fisk, John and Montgomery, C. (2009) Evidence for selective executive function deficits in ecstasy/polydrug users. Journal of Psychopharmacology, 23 (1). pp. 4050. ISSN 02698811
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John E Fisk
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Evidence for selective executive function deficits in ecstasy/polydrug users.
John E. Fisk, PhD
University of Central Lancashire,
Catharine Montgomery, PhD
Liverpool John Moores University
Running head: selective executive function deficits
Corresponding author:
Dr John E Fisk
Department of Psychology
University of Central Lancashire
Preston PR1 2HE
United Kingdom
Tel 44 (0) 1772 894465
Fax 44 (0) 1772 892925
e-mail: [email protected]
John E Fisk
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Abstract
Previous research has suggested that the separate aspects of executive functioning
are differentially affected by ecstasy use. While the inhibition component executive
process appears to be unaffected by ecstasy use, it is unclear whether this is true of heavy
users under conditions of high demand. Tasks loading on the updating component
executive process have been shown to be adversely affected by ecstasy use. However, it
remains unclear whether the deficits observed reflect the executive aspects of the tasks
and whether they are domain general in nature affecting both verbal and visuo-spatial
updating. Fourteen heavy ecstasy users, 39 light ecstasy users and 28 non users were
tested on tasks loading on the inhibition executive process (random letter generation) and
the updating component process (letter updating, visuo-spatial updating and computation
span). Heavy users were not impaired in random letter generation even under conditions
of high demand. Ecstasy related deficits were observed on all updating tasks. These
deficits remained statistically significant following controls for various aspects of
cannabis use. It was concluded that the inhibition component executive process is
unaffected by ecstasy use even among heavy users. By way of contrast, the updating
component process appears to be impaired in ecstasy users with the deficit apparently
domain general in nature.
Keywords: ecstasy (MDMA), inhibition, updating, executive, random generation,
visuo-spatial.
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There is cause to believe that among the many illicit drugs commonly in use, ecstasy in
particular causes long term impairment to cognitive processes through its effects on the
serotonin system (Gouzoulis-Mayfrank & Daumann 2006; Morgan, 2000; Reneman et al
2006). Morgan (2000, page 234) has noted that ‘it has been proposed that it [serotonin]
may play an orchestrating role in cognition’. More specifically, the serotonin system is
believed to underpin working memory processes through its modulation of the
dopaminergic systems that support prefrontal executive processes (Luciana, Collins, &
Depue, 1998; Robbins 2000).
Recent investigations of executive functioning suggest that the central executive
is fractionated. For example, Miyake et al. (2000) studied the separability of three
supposed executive functions: mental set shifting (“shifting”), information updating and
monitoring (“updating”), and inhibition of pre-potent responses (“inhibition”). Structural
equation modelling revealed that the three executive functions were clearly separate and
appeared to contribute differentially to performance on higher level tasks that are known
to be reliant on prefrontal cortical resources. For example, the Wisconsin Cart Sort Task
(WCST) was linked to the shifting component, the Tower of Hanoi to the inhibition
component, random number generation to both the inhibition and updating components,
and operation span to the updating component.
Using factor analysis, Fisk and Sharp (2004) provided further support for Miyake
et al’s model, finding that reading span and computation span (analogous to Miyake et
al’s operation span task), letter updating (Morris & Jones, 1990) and a visuo-spatial serial
recall task (Brooks, 1967) all loaded on a single factor corresponding to Miyake et al’s
updating executive process. Aspects of random letter generation loaded on a separate
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factor corresponding to Miyake et al’s inhibition executive process, while WCST
measures loaded on a third factor (equivalent to Miyake et al’s switching executive
process). Additionally, a fourth factor emerged which Fisk and Sharp termed access to
long-term memory and on which verbal fluency tasks loaded.
Previous research from our laboratory (Fisk et al, 2004; Montgomery et al, 2005;
Wareing et al 2004) utilising Miyake et al’s conceptual framework, revealed ecstasy-
related deficits in memory updating (computation span and letter updating), and access to
long-term memory (verbal fluency). No differences were observed on tasks assessing the
switching (the plus-minus and number letter task) and inhibition (random letter
generation) component processes. However inconsistencies in this area of research have
emerged. From our own laboratory, while Wareing, et al (2000) found ecstasy users to be
impaired in random letter generation, we have failed to obtain this outcome in subsequent
studies (Fisk, et al, 2004; Montgomery, et al, 2005). Similarly the ecstasy-related deficits
in relation to the updating executive component process that emerged from our own
research (Montgomery et al, 2005) have not have been replicated by Dafters (2005) using
the keeping track task.
Clearly these inconsistencies require explanation and warrant further research.
Wareing et al’s (2000) participants had an atypically high estimated lifetime ecstasy dose
exceeding 1000 tablets and the random letter generation task used, restricted participants
to producing only consonants. In our later study (Fisk et al, 2004) those we tested had an
appreciably lower lifetime exposure to the drug and we administered the original version
of the task (Baddeley 1966) in which any letter of the alphabet may be produced. It is
possible therefore that ecstasy might impair the inhibition component process but only at
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high does and only when the processing load is substantial. To resolve this ambiguity, it
would be desirable to repeat the consonants only random generation task on a group of
high dosage users in order to replicate our previous findings.
Questions have also emerged concerning our previous results which demonstrated
ecstasy-related updating component executive deficits. First at six letters, the
maintenance element of the updating task exceeded the letter span of the majority of
participants that we tested. Consequently many participants may have adopted a free
recall recency based strategy negating the need for updating (Collette et al, 2006; Smith-
Spark et al, 2003). It would be desirable to repeat our original experiment ensuring that
the maintenance component of the task does not exceed the letter span of our participants.
Second, we have recently demonstrated ecstasy-related deficits in visuo-spatial working
memory tasks (Wareing et al, 2004; 2005) although it is unclear which executive
component processes may be implicated in this regard. Recent conceptualisations of
executive function tasks suggest the processing component of these is domain general
(e.g., Bayliss et al 2003; Kane et al , 2004). If the updating component does reflect some
domain general process it would be expected that the impairments that we have observed
in verbal updating would also manifested in visuo-spatial updating .
Method
Design and Analysis.
For the random letter generation task, a mixed design was used with rate of letter
generation (with three levels; 4 seconds, 2 seconds, and 1 second)) within participants
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and ecstasy users group (with three levels; heavy, light, and nonuser) between
participants. Dependent variables were the number of alphabetically ordered pairs,
number of repeated pairs, redundancy, and the number of vowel intrusions. With regard
to the updating executive component tasks, verbal and spatial updating, and the
computation span task, a multivariate design was used with user group (3 levels) between
participants and the three measures of executive functioning as dependent variables.
Orthogonal contrasts were employed in which heavy ecstasy users were compared to
light users and the two ecstasy user groups combined compared with nonusers.
Orthogonal contrasts were used as they allow inter-group comparisons to be made while
controlling the Type 1 error rate without the need to adjust the alpha level per comparison
(Tabachnick & Fidell, 2001).
Participants.
Fourteen heavy ecstasy users (mean age 22.86; 9 male), 39 light ecstasy users
(mean age 21.41; 19 male) and 28 non-user controls (mean age 20.71; 7 male) took part
in the study. The heavy users group comprised all of those users with an estimated
lifetime dose exceeding 400 tablets, (mean 1000.21, s.d., 786.41). Light users were those
with an estimated lifetime dose of less than 400 tablets, (mean 149.69, s.d., 96.91). The
cut off point of four hundred tablets was determined by trial and error so as to produce a
high use group with a mean lifetime dose of 1000 tablets as this was the level of exposure
characterising the ecstasy users in our previous study (Wareing et al 2000). Nonusers
were those who indicated that they had never used ecstasy. Participants were recruited via
direct approach to university students, and the snowball technique (Solowij et al, 1992).
With 14 ecstasy users, the present sample is sufficient to detect a difference of 1.25 for α
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= .05 and β =.20 (Hinkle et al, 1994). Participants were requested to refrain from ecstasy
use for at least 7 days and ideally 10 days prior to testing. The mean period of abstinence
was actually 22 and 27 weeks for heavy users and light users respectively; median
abstinence period 5.5 and 4 weeks respectively. Participants were also requested not to
use any other illicit drugs for at least 24 hours and ideally for 7 days prior to testing.
Measures.
Patterns of drug use and other relevant lifestyle variables were investigated via
means of a background questionnaire. The questionnaire gauged the use of ecstasy and
other drugs, as well as age, years of education, general health and other relevant lifestyle
variables. In relation to other drugs, participants were asked a range of questions
including frequency and duration of use and the last time that they had used each drug.
Participants were also questioned concerning their history of drug use, and using a
technique employed by Montgomery, et al (2005), these data were used to estimate total
lifetime use for each drug. Average weekly dose and the amount of each drug consumed
within the previous 30 days were also assessed. Fluid intelligence was measured via
Raven’s Progressive Matrices (Raven et al, 1998), and premorbid intelligence was
assessed via the National Adult Reading Test (NART, Nelson, 1982).
Letter Span: Consonants were presented sequentially on a computer screen for
1.25 seconds. Participants were then required to recall the letters in the order in which
they were presented. The task commences with three sets of two letters, and is then
increased to three sets of three, four, five etc., until the individual fails on at least two out
of three trials. Digit span was administered in a similar manner except that the letters
were replaced with digits.
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Updating. Updating has been used extensively as a measure of prefrontal
executive functioning. (see for example, Fisk & Sharp, 2003; 2004; Miyake et al, 2000;
Morris & Jones, 1990; Smith-Spark & Fisk, in press; van der Linden et al 1999). The
participant’s letter span, ‘n’, was determined. In the consonant updating task the
participant was presented with a random sequence of between n and n+6 consonants on a
computer screen. Twenty-four such lists were presented, and in each case, the participant
was unaware of the number of consonants to be presented. The task was always to recall
the most recent ‘n’ consonants in the order in which they were presented. (Thus the
maintenance element of the task was limited to the individual’s actual span. This
contrasts favourably with our previous study where at six letters the maintenance
requirement exceeded the span of most of our participants.) The participant experienced
six trials at each of the four list lengths: n, n+2, n+4, and n+6 items. The order in which
the lists were presented was randomised. A single composite score of updating was
calculated by computing the average number correct for each serial position over the 6
trials at each list length. The resulting figures were then averaged over list length and
serial position.
The spatial updating task was analogous to consonant updating except that it
involved the serial recall of cells that were highlighted sequentially, one at a time, in a
Corsi style display. The participant’s spatial span, ‘n’, was determined. In the updating
task the participant was presented with a random sequence of between n and n+6 cells
highlighted on a computer screen in a Corsi style configuration. Twenty-four such
sequences were presented, and in each case, the participant was unaware of the number of
cells that were highlighted. The task was always to recall the most recent ‘n’ cells in the
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order in which they were presented. As in the consonant task, the participant experienced
six trials at each of the sequence lengths. The order in which the lists were presented was
randomised. A single composite score of updating was calculated using the same
procedure as outlined for the consonant updating task.
Computation Span. Computation span has been used extensively as an indicator
of working memory functioning in the cognitive ageing literature (Fisk & Warr, 1996;
Salthouse & Babcock, 1991) and it is similar to the operation span measure used by
Miyake, et al (2000) in their investigation of executive processes. Participants were
required to solve a number of arithmetic problems (e.g., 4+7 = ?) by circling one of three
multiple-choice answers as each problem was presented. They were also required to
simultaneously remember the second digit of each presented problem. At the end of each
set of problems the second digits had to be recalled in the order in which they were
presented. The number of arithmetic problems that the participant had to solve, while at
the same time remembering each second digit, gradually increased as the test proceeded.
For each of the first three trials only a single problem was presented. For the next three
trials, two problems were presented. Subsequently, the number of problems presented per
trial increased by one every third trial. In order to proceed, the participant was required to
be correct in at least two of the three trials at the current level. Computation span was
defined as the maximum number of end digits recalled in serial order, with the added
requirement that the corresponding arithmetic problems had been solved correctly. In
order to take account of individual differences in the non-executive maintenance
component of the task, the load on executive resources was computed as the percentage
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difference between the computation and digit span scores. Large percentage differences
are indicative of poor executive functioning.
Random letter generation. A computer display and concurrent auditory signal was
used to pace responses. Participants were asked to speak aloud a letter every time the
signal was presented. They were told to produce only consonants (i.e., to avoid the letters
a, e, i, o, and u); to avoid repeating the same sequence of letters; to avoid producing
alphabetically ordered sequences; and to try to speak each letter with the same overall
frequency. Individuals attempted to produce three sets of 100 letters; one set at a rate of
one letter every 4 s, a second set at one letter every 2 s, and a third at one letter every 1 s.
The order in which the sets were generated was randomised. The experimenter recorded
the responses on an answer sheet. The test yields four scores. First, the number of
alphabetically ordered pairs; second, a repeat sequences score corresponding to the
number of times that the same letter pair is repeated; third, a “redundancy” score, which
measures the extent to which all 26 letters of the alphabet are produced equally often (0%
being truly random); and fourth, the number of vowel intrusions. In all cases, higher
scores are indicative of poor performance.
Procedure.
Participants were informed of the general purpose of the experiment, and written
informed consent was obtained. The tests were administered under laboratory conditions,
and a computer running MS-DOS was used for the computer based tasks. The tests were
administered in the following order: background questionnaire, random letter generation,
digit, letter, and spatial span, computation span, letter and spatial updating, Raven’s
progressive matrices, and the NART. Participants were fully debriefed, paid £15 in store
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vouchers, and given drugs education leaflets. The study was approved by the Ethics
Committee of Liverpool John Moores University, and was administered in accordance
with the Declaration of Helsinki.
Results
There were no significant differences between the groups on the Raven’s and
NART measures and the number of years of education. Inspection of Table 1 reveals that
age differed significantly between the groups. Tukey’s test revealed that heavy users were
significantly older than the other two groups, p<.01 and p<.05 in relation to nonusers and
light users respectively. Light users and nonusers did not differ significantly from each
other. Table 1 also contains mean simple span scores (digit, letter and spatial) for each of
the three groups. Ecstasy users were unimpaired on these measures in fact scoring
marginally higher compared to non ecstasy users.
<Insert Table 1 about here>
The vast majority of all of the groups had previous exposure to cannabis. Ninety-
three percent of heavy ecstasy users, 87% of light users and 75% of non ecstasy users
indicated that they had used cannabis. Cocaine use was also common among ecstasy
users. All heavy ecstasy users and 72% of light ecstasy users indicated that they had
previously used cocaine. However, only 11% of nonusers had had any exposure to this
drug. Other drugs that had been previously used included amphetamine and LSD but use
of these was less prevalent and limited to the ecstasy user groups. Sixty-four percent of
heavy ecstasy users and 33% of light ecstasy users indicated that they had previously
used amphetamine. The equivalent figures for LSD were respectively, 64% and 13%. For
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those drugs where it was possible to quantify the level of use a number of relevant
measures are set out in Table 2. Heavy ecstasy users also consumed substantial quantities
of cocaine and cannabis. Light ecstasy users also used these drugs but to a lesser extent.
Among non ecstasy users the only illicit drug that was used was cannabis but the
exposure to this drug was of a lower order compared to the other two groups. (Three non
ecstasy users indicated that they had used cocaine on one or two previous occasions but
were unable to quantify the amount.) For the most part the measures of drug use were not
normally distributed. In many instances the median response was zero and more generally
the distributions were positively skewed. In addition the group variances were generally
heterogeneous. As a consequence nonparametric analyses were used with the results
revealing that most of the indicators of drug use set out in Table 2 differed significantly
between the groups. With regard to differences between the two ecstasy user groups,
heavy users scored significantly higher than light users in terms of total lifetime and
average weekly consumption of both cannabis and cocaine. Heavy users had used ecstasy
and cocaine significantly longer than light users although length of cannabis user did not
differ significantly between the two ecstasy user groups. Also there were no significant
differences between heavy and light ecstasy users in terms of their use of illicit drugs in
the previous 10 and 30 days.
<Insert Table 2 about here>
Outcomes for the different aspects of executive functioning are set out in Table 3. In all
aspects of random letter generation the scores were similar between the groups. Mixed
ANOVA was used with group between participants and rate of letter generation within.
Consistent with the trends evident in the means, none of the group effects were
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statistically significant, for each of the four analyses (redundancy, repeat sequences,
alphabetical sequences and vowel intrusions), F < 1. Also in each case the interaction
between group and rate of letter generation was non significant, again in each of the four
analyses, F < 1. The number of letters produced was close to ceiling (i.e., 100 letters) for
all groups at the four and two second generation rates. Although performance declined at
the one second rate this was equally apparent for all groups. The maximal number of
letters generated by most participants at the four and two second rates prevents
meaningful analysis. However, ANOVA with group between participants and the number
of letters generated at the one second rate as the dependent variable revealed no
significant difference between the groups, F < 1. Thus to summarise the present results
provide no evidence of ecstasy-related differences in the inhibition component executive
process on which random letter generation is known to load.
<Insert Table 3 about here>
The percentage reduction in capacity associated with the concurrent processing
component of the computation span task is set out in Table 3 along with the outcomes for
the spatial and verbal (consonant) updating tasks. All three measures are believed to load
on the updating executive component process. For each of these three indicators of
executive functioning non ecstasy users outperform both ecstasy user groups. Non users
exhibit substantially lower costs in relation to the processing component of the
computation span task. They also exhibit more efficient updating both in relation to
verbal and visuo-spatial stimuli. MANOVA with user group between participants and the
three measures of the updating component executive process as dependent variables
revealed a significant multivariate group effect, Wilks’ lambda = .836, F(6,150)=2.34,
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p<.05. Regarding the univariate outcomes, the group differences were statistically
significant for both computation span and spatial updating, with F values of 3.23 and 3.97
respectively on 2,77 degrees of freedom, p<.05 in both cases. The group difference for
the verbal updating task failed to reach significance, F(2,77) = 2.23, p>.05. Difference
contrasts revealed that nonusers performed significantly better than the combined user
groups on the computation span and spatial updating measures, p<.05 and p<.01
respectively, the difference approached significance for the verbal updating task, p=.091.
However, the contrasts revealed that the two user groups did not differ from each other
on any of the updating measures, p>.05 in all cases.
As inspection of Table 2 revealed, ecstasy users (especially heavy users)
consumed considerably more cannabis compared to non ecstasy users both in terms of
long term and recent use. It is possible therefore that various aspects of cannabis use may
have accounted for the ecstasy-related group differences that were obtained on the
updating executive component measures. To control for this possibility, the MANOVA
was repeated with the two long term (total lifetime consumption and average weekly
consumption) and two short term measures of cannabis use (amount used in the last 10
and 30 days) as covariates. The multivariate group effect remained significant, Wilks’
lambda = .793, F(6,118)=2.42, p<.05. Regarding the univariate outcomes, the group
differences were statistically significant for verbal updating and spatial updating with F
values of 3.86 and 3.62 respectively on 2,61 degrees of freedom, p<.05 in both cases. The
group difference for the computation task approached significance, F(2,61) = 3.02,
p=.056. Difference contrasts revealed that nonusers performed significantly better than
the combined user groups on all three measures, p<.05 in all cases, while the two user
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groups did not differ significantly from each other on any of the measures, p>.05 in all
cases. Tests for homogeneity of regression were conducted for each covariate with
respect to each of the dependent variables yielding a total of 12 analyses. In 11 of the 12
cases, homogeneity of regression was obtained, p>.05, for the covariate by group
interaction in all cases. In one case homogeneity of regression was not obtained. This was
in relation to average weekly cannabis consumption and the computation span measure
where the covariate by group interaction yielded F(2,62) = 4.81, p<.05.
The absence of cocaine users among the non-ecstasy users makes it impossible to
control statistically for the potentially confounding effects of cocaine use since it is not
possible to test for homogeneity of regression. To evaluate the extent to which cocaine
use (as well as ecstasy and cannabis use) is associated with performance on the updating
executive component measures we examined the correlations (Spearman’s rho) between
the different aspects of drug use and the outcomes on the updating measures. The results
are set out in Table 4. It is clear that only aspects of ecstasy use are significantly
correlated with the updating executive component measures. None of the aspects of
cocaine use are associated with statistically significant correlations.
<Insert Table 4 about here>
Discussion
No significant ecstasy-related differences were observed in the random letter
generation task. The consonants only version used here was the same as that used in our
early research and as noted above this was associated with a significant group difference
in our initial study (Wareing et al, 2000). Mean lifetime consumption of ecstasy tablets
exceeded 1000 in that study which is appreciably higher than was apparent in our
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subsequent research. Furthermore there is clear evidence that restricting the letter set to
consonants only, caused particular problems for the ecstasy users groups in Wareing et
al’s (2000) study as they produced significantly more vowel intrusions under all
generation rates. Thus it had been conjectured that deficits might be found in the present
study among heavy chronic users on the consonants only version of the task. However,
the results presented here demonstrated that this was not the case. The basis for the
significant group difference in our original study (Wareing et al, 2000) remains unclear.
With just 10 participants in each group, the sample sizes were small. Furthermore in our
previous study, we did not assess participants on measures of intelligence. Thus it
remains possible that the differences we observed might have been due to some
premorbid factor other than drug use. The fact that the present study along with other
recent results from our laboratory (Fisk et al 2004; Montgomery et al 2005) have not
revealed ecstasy related deficits in random letter generation suggest that this aspect of
cognitive functioning is unimpaired. Since random letter generation is an established
measure of the inhibition component executive process, it would seem reasonable to
conclude that ecstasy use does not adversely affect this aspect of cognition.
Research from our own laboratory has suggested that ecstasy use may be
associated with deficits in the updating executive component process. Two measures of
the updating function appear to be subject to ecstasy-related impairment, computation
span and letter updating (Montgomery et al, 2005). However, with regard to the latter, in
our previous study, participants were required to maintain a load of six letters while
concurrently performing the updating task. It appears that this load exceeded the letter
span of the majority of participants and for these individuals it would have been
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impossible to perform the maintenance element of the task. This raises the question of
whether any serial rehearsal element and concurrent updating activity was actually
occurring. It is possible that participants may have adopted a free recall strategy with a
reliance on the recency component of the process. Baddeley and Hitch (1993) have
argued that the recency phenomenon is distinct from the maintenance and processing
functions of working memory. Thus while we have demonstrated an ecstasy related
deficit in letter updating, this may not in fact reflect an executive function deficit. In an
important early study of the updating process Morris and Jones (1990) addressed this
problem by running two experiments, the first with a load of six letters and the second
with a load of four letters. However, reducing the load to four letters is not without
problems as it makes it possible for those individuals with large letter spans to avoid
updating all together by encoding and serially rehearsing the entire sequence where the
presented sequence length allows this. In order to address this problem, in the present
study participants were required to maintain a load that was equivalent to their letter span.
The orthogonal difference contrasts revealed that following control for group differences
in cannabis consumption ecstasy users performed worse than nonusers on all three
measures of the updating component executive process, including the letter updating task,
computation span, and visuo-spatial updating. Thus it can be argued with some degree of
confidence that ecstasy users are impaired on this executive component function.
It has been argued that the storage aspects of the working memory system are
domain specific while processing is domain-general in nature (e.g., Bayliss et al 2003;
Kane et al , 2004). Thus verbal and visuo spatial information would be stored by
functionally separate systems but the processing component of tasks utilising this
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information would be domain-general in nature. Given that ecstasy users have been found
to exhibit deficits in verbal updating, the domain general nature of the process would
imply that deficits should also be apparent in updating visuo-spatial information. In our
previous research we have found ecstasy users to be impaired in a visuo-spatial complex
span task (Wareing et al, 2004; 2005). While analogous verbal tasks have been found to
load on the updating component executive process (Miyake et al, 2000; Fisk & Sharp,
2004), it is unclear whether this applies to the visuo-spatial working memory task that we
employed previously. The present study has used an analogue of the verbal updating task,
in which individuals were required to maintain and update a spatial sequence and it was
established that ecstasy users were significantly impaired on this task relative to nonusers.
The presence of deficits on both the verbal and visuo-spatial updating tasks is consistent
with Baylis et al (2003) and Kane et al’s (2004) view of working memory and it may be
that the deficits observed reflect an ecstasy-related impairment in this domain general
updating process.
The present findings may be viewed in the context of recent neuroscience
evidence. It is known that MDMA affects both serotonergic and dopaminergic systems
(e.g. Kish et al, 2002). Functional neuroimaging studies indicating that ecstasy/polydrug-
related neurotransmitter changes may be concentrated in the dorsolateral and parietal
regions of the prefrontal cortex (Cohen et al, 1996), and in addition may give rise to
significantly lower grey matter concentrations in multiple brain regions (bilateral BA 18
and cerebellum, left BA 21 and left BA 45, as well as the midline brainstem; Cowan et al.
2003). Memory updating has been particularly linked to the dorsolateral prefrontal cortex
(Goldman-Rakic, 1996) while performance on the letter-updating task is most strongly
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associated with the left fronto-polar cortex (Collette et al, 2006; Van-der-Linden et al,
1999). So it is likely that the deficits observed in the present study reflect reduced
serotonergic/dopaminergic functioning in specific regions of the prefrontal cortex.
As with most studies in this area, a number of limitations need to be
acknowledged. Due to the quasi-experimental design of the study, it is possible that the
groups in each study may have differed on some variable other than ecstasy use. The
groups differed significantly in age and although the tests administered are subject to age-
related decline, this does not typically occur until old age. None of the participants tested
in the present study were more than 27 years old. Group differences in other variables
such as general health, nutrition, or some premorbid condition predating drug use
(Verheul, 2001) cannot be ruled out. Furthermore, due to limited resources we were
unable to provide an objective measure of recent drug use (e.g. from hair or urine
samples). However, most published studies testing cognitive deficits among ecstasy users
have not used these techniques (e.g. Fox et al, 2002; Morgan, 1998; Rodgers, 2000). We
were able to statistically control for group differences in both recent and longer term
aspects of cannabis use. Furthermore, aspects of ecstasy use were more closely correlated
with the cognitive outcomes compared to the equivalent correlations with cocaine use.
However it must be acknowledged that a minority of the ecstasy users had in the past
used amphetamine and a small number LSD. We cannot therefore entirely exclude the
possibility that these drugs may have played some role in the results that were obtained.
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Table 1: Background Variables
Heavy Ecstasy users
Light Ecstasy Users
Non Ecstasy Users
F(2,78)
Mean S.D. Mean S.D. Mean S.D.
Age (years)
22.86 2.38 21.41 2.05 20.71 1.37 5.91**
Years of Education
15.11 2.66 14.87 3.11 15.55 2.24 < 1
Raven’s Progressive Matrices (maximum 60)
45.86 7.19 46.74 5.96 49.36 5.06 2.25
NART (maximum 50)
27.86 8.39 28.72 5.67 29.14 5.02 < 1
Digit Span
6.86 1.03 6.89 1.17 6.60 1.47 < 1
Letter Span 5.21 1.05 5.46 0.94 5.04 0.84 1.75
Spatial Span 4.57 0.85 4.92 0.77 4.57 0.96 1.71
** p<.01
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Table 2: Indicators of Illicit Drug Use
Heavy Ecstasy Users Light Ecstasy Users Non Ecstasy Users
Median Mean S.D. n Median Mean S.D. n Median Mean S.D. n Total Use Ecstasy (Tablets) 6.8.00 1000.21 786.41 14 142.00 149.69 96.91 39 0.00 0.00 0.00 28 Cannabis (joints) 5200.00 6383.27 5830.32 11 320.00 1779.51 2971.07 37 22.00 262.13 507.44 23 Cocaine (grams) 75.75 127.52 144.64 6 0.00 17.51 35.84 21 0.00 0.00 0.00 25 Average Weekly Dose Ecstasy (tablets) 2.87 3.49 2.05 14 0.73 0.99 0.68 38 0.00 0.00 0.00 28 Cannabis (joints) 15.08 15.59 12.76 11 2.40 5.96 9.97 35 0.17 1.60 2.84 23 Cocaine (grams) 0.44 0.52 0.47 6 0.00 0.14 0.29 21 0.00 0.00 0.00 25 Length of use (weeks) Ecstasy 271.00 300.82 136.12 14 148.00 176.29 108.55 39 - - - - Cannabis 260.00 342.14 184.14 13 268.00 283.56 145.16 33 172.00 172.83 106.63 21 Cocaine 217.22 240.63 136.35 14 121.00 137.65 79.50 27 - - - - Drugs Used During the 30 days Prior to Testing
Ecstasy 0.00 2.61 4.09 14 0.50 1.73 2.60 39 0.00 0.00 0.00 28 Cannabis 24.00 56.31 75.15 13 3.00 22.80 45.00 38 0.00 7.04 29.30 26 Cocaine 0.25 0.45 0.55 10 0.00 0.25 0.66 30 0.00 0.00 0.00 27 Drugs Used During the 10 days Prior to Testing
Ecstasy 0.00 0.68 1.49 14 0.00 0.32 0.86 39 0.00 0.00 0.00 28 Cannabis 0.50 6.75 12.50 14 0.00 2.79 6.03 39 0.00 1.14 3.57 28 Cocaine 0.00 0.10 0.18 14 0.00 0.08 0.24 39 0.00 0.00 0.00 28
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Table 2 continued
Overall Group Effect: Kruskal-Wallace (χ)
Heavy Ecstasy Users versus Light Users: Mann-Whitney U value
Total Use Ecstasy (Tablets) χ(df=2, N=81) = 70.26*** 0.00*** Cannabis (joints) χ(df=2, N=71 )= 16.65*** 113.50* Cocaine (grams) χ(df=2, N=52) = 28.37*** 16.50** Average Weekly Dose Ecstasy (tablets) χ(df=2, N=80) = 65.49*** 46.00*** Cannabis (joints) χ(df=2, N=69) = 13.37** 108.50* Cocaine (grams) χ(df=2, N=52) = 27.43*** 21.00* Length of use (weeks) Ecstasy 115.50** Cannabis χ(df=2, N=67) = 10.29** 178.50 Cocaine 91.00** Drugs Used During the 30 days Prior to Testing
Ecstasy χ(df=2, N=81) = 19.07*** 272.00 Cannabis χ(df=2, N=77) = 9.77** 205.50 Cocaine χ(df=2, N=67) = 13.65** 109.00 Drugs Used During the 10 days Prior to Testing
Ecstasy χ(df=2, N=81) = 5.80 251.50 Cannabis χ(df=2, N=81) = 6.25* 235.00 Cocaine χ(df=2, N=81) = 7.48* 246.00
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Table 3 Performance on Executive Measures
Heavy Ecstasy users
Light Ecstasy Users
Non Ecstasy Users
Mean S.D. Mean S.D. Mean S.D.
Random Generation Redundancy 4 second 4.78 2.53 4.00 1.72 4.49 2.14 2 second 5.95 1.94 5.01 2.05 5.11 2.26 1 second 7.05 3.00 7.17 3.02 7.37 2.15 Repeat Sequences 4 second 16.00 3.26 14.05 4.76 14.14 4.28 2 second 16.86 3.61 16.72 6.41 16.54 4.77 1 second 19.07 8.40 18.23 5.89 18.39 6.15 Alphabetic Sequences 4 second 5.07 2.50 4.62 3.88 3.79 3.37 2 second 6.79 3.58 7.10 5.08 6.96 4.62 1 second 10.86 5.55 11.87 6.51 12.11 6.44 Vowel Intrusions 4 second 0.71 0.83 1.23 1.86 1.18 1.49 2 second 1.29 1.49 1.49 2.76 1.61 2.06 1 second 2.79 3.02 3.18 3.43 3.04 2.25 Number of Letters Generated 4 second 100.14 0.36 100.15 0.43 100.11 0.50 2 second 99.93 1.00 99.15 3.08 98.79 3.08 1 second 90.00 11.73 89.74 9.51 88.43 10.15 Computation Span (% cost)
49.04 28.75 41.32 25.21 29.43 23.00
Consonant Updating
3.99 0.71 3.83 0.83 4.22 0.61
Spatial Updating 4.01 0.56 4.03 0.66 4.48 0.75
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Table 4. Correlations between Aspects of Illicit Drug Use and Updating Executive
Component Measures
Computation Span
Verbal Updating
Spatial Updating
n
Total Use Ecstasy (Tablets) .295** -.234* -.235* 80 Amphetamine Cannabis (joints) .040 .035 -.020 70 Cocaine (grams) .246 .014 -.183 51 Average Weekly Dose Ecstasy (tablets) .316** -.279* -.288** 79 Amphetamine Cannabis (joints) .011 .036 -.020 68 Cocaine (grams) .251 .013 -.188 51 Length of use (weeks) Ecstasy .075 .147 .081 53 Amphetamine Cannabis -.121 -.127 -.031 43 Cocaine .183 .079 -.017 66 Drugs Used During the 30 days Prior to Testing
Ecstasy .117 -.125 -.305** 80 Amphetamine Cannabis .106 .039 -.055 76 Cocaine .024 .069 -.166 66 Drugs Used During the 10 days Prior to Testing
Ecstasy -.084 .008 .036 80 Amphetamine Cannabis .123 -.093 -.194 80 Cocaine .032 .009 -.169 80
** p<.01; * p<.05